The object of this study is to elucidate mechanisms of differentiation of B-cell precursors by examining features of differentation arrest in pre-B-cell malignancies. The phenotype of 80 leukemias and lymphomas was determined by immunofluorescence techniques. Several FCC lymphomas demonstrated partial differentiation in that they contained large accumulations of intracytoplasmic immunoglobulin. Forty-one lymphomas and leukemias were examined for natural killer cell phenotype by staining for surface and cytoplasmic antigens detectable by the monoclonal antibody, HNK-1. Very few cells were positively identified, and no lymphomas or leukemias of NK phenotype were found. A leukemic cell line, Mays FI2, was established in methyl cellulose culture. The interesting feature of these cells is that they lack surface Ig and light chain expression but contain cytoplasmic gamma chains, suggesting a pre-B switch from micro to gamma. DNA extracts from this and other lines are being analyzed for Ig gene rearrangements, especially for C-micro gene deletions, using cDNA probes. IL-1, which has been shown to stimulate pre-B-cell differentiation in mice, was prepared from human monocytes and used to stimulate fresh ALL cells and leukemic cell lines. A single ALL showed no proliferative, but moderate, differentiative response. Studies of the effect of IL-1 and receptors for IL-1 on other human leukemic cells are underway. Additional studies for the coming year include: (1)\examination of the membrane and secretory physiochemical properties of pre-B leukemic cell micro and gamma chains; (2)\subcloning of leukemic and lymphomatous cells to explore the contribution of cell cycle to differentiation arrest; (3)\hybridization of leukemic cells with nonsecretory myeloma cells to determine the effects of fusion on surface Ig and light chain expression; and (4)\exploration of growth factor requirements of pre-B and B leukemic cells. (AB)